DESCRIPTION: A major gap in current knowledge deals with the identification and characterization of genes involved in the normal development and formation of premaxilla. This is of particular importance due to its relationship with the formation of clefts of the lip and/or palate, CL(P). The long-term goals of this project are to identify genes involved in the development of the premaxilla and to determine which of these genes have an altered pattern of expression in mice with CL(P). The genes will be isolated using a subtractive hybridization technique called Representational Display Analysis (RDA). RNA will be isolated from the midfacial region of the twirler mutant mice. All twirler homozygotes exhibit clefts of the lip and/or palate. This RNA will be used as the driver against RNAs isolated from the same region of wild type mice (no clefts). The specific aims are: 1) to isolate cDNAs coding for downstream genes of the twirler that are required for normal midfacial development, and 2) to perform an initial characterization of the cDNA clones obtained. This project should increase the understanding of factors regulating growth of the craniofacial complex, knowledge which is necessary for the eventual treatment of craniofacial disorders, such as clefts of the lip and/or palate.